55 research outputs found
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Beauty in Buildings: How Beauty and Inspiration Impact Building Energy Performance
Consideration of beauty in the built environment is growing within the building sector as the broader concept of sustainable building design replaces the more narrowly defined concepts of high performance or green building. Similarly, as building design teams become more integrated, pairing architects, engineers, construction managers, and other professionals, the concepts of beauty and energy performance are approached collectively. In research led by ml Robles, NCARB Architect at the PatternMapping institute, characteristics representative of beautiful buildings were identified and metrics and criteria relating these beauty characteristics to building energy performance were compiled to form a qualitative evaluation tool. A sample of 35 case studies contrasting high performing with inspiring and high performing buildings were evaluated for building performance relative to both beauty and energy using the qualitative evaluation tool. Results indicated that the inspiring and high performing buildings included building systems or features that more consistently provide an experienced connection between the occupants, the built environment, and ultimately the surrounding environment.Building energy models representing distinguishing building systems or features identified from the qualitative evaluation were developed for quantitative evaluation of energy performance through energy simulation. Relative importance to beauty and energy performance of each of the building systems or features was determined and presented as color-scaled quantitative references. The color-scaled references illustrated that building systems or features that exhibit density - combination of multiple systems - in their designs offered better performance relative to both beauty and energy.The qualitative evaluation tool and the color-scaled quantitative references developed in this research provide useful tools for architects and engineers seeking to design built environments that are both inspiring and high performing
Updating the Kentucky Contract Time Determination System
The Federal Highway Administration requires State Transportation Agencies to have a formal method to estimate contract time for highway construction projects. To meet this requirement many states use an integrated scheduling system to estimate project durations based on assumed productivity rates and generic job logic. The current work investigated the accuracy of two of these systems found that both systems accuracy in predicting the duration of Kentucky Transportation Cabinet projects was greater than +200%. In response to this poor accuracy, a parametric project duration estimating tool was developed based on a multivariate regression analysis of bid item quantities and engineering and construction estimate. Five regression models were develop to estimate contract time for large projects (great than 1,000,000) as it appears that the duration of small projects is determined by factors outside of bid item quantities
Komikiak aztertzeko gida bat
40 p.Fikziozko narrazioa funtsezkoa izan da zinemaren hastapenetik, eta gidoia da zehazki kontakizun horren lehen hazi edo abiapuntua. Irudiek euren kabuz komunikatzeko duten ahalmena dela eta, zinema gidoiak ikus-entzunezko hizkuntzak bere-berezko dituen ezaugarriak eta teknikak gaineratu dizkie ahozko eta idatzizko narrazio tradizionalen baliabideei. Berezitasun horrek gidoigintzari buruzko askotariko testuak eta argitalpenak eragin ditu azken urteotan. Horien artean nabarmenenak eta esanguratsuenak aukeratzea, eta haien edukiak eta irakaspenak biltzea da, hain justu, jarraian datozen orrialdeen xedea: fikziozko gidoigintzari buruzko ikuspegi orokorra eskaintzea eta, nagusiki, lehen aldiz euskaraz egitea.Edizio hau Eusko Jaurlaritzak eratzen duen Ikerketa Talde Finkoen Sarean kokaturik dagoen eta Euskal Herriko Unibertsitateak onartu duen LAIDA (Literatura eta Identitatea) Ikerketa-taldearen (IT 1397/19, GIU 20/26) eginkizunen barnean egin da
Validity and worth in the science curriculum: learning school science outside the laboratory
It is widely acknowledged that there are problems with school science in many developed countries of the world. Such problems manifest themselves in a progressive decline in pupil enthusiasm for school science across the secondary age range and the fact that fewer students are choosing to study the physical sciences at higher levels and as careers. Responses to these developments have included proposals to reform the curriculum, pedagogy and the nature of pupil discussion in science lessons. We support such changes but argue from a consideration of the aims of science education that secondary school science is too rooted in the science laboratory; substantially greater use needs to be made of out-of-school sites for the teaching of science. Such usage should result in a school science education that is more valid and more motivating and is better at fulfilling defensible aims of school science education. Our contention is that laboratory-based school science teaching needs to be complemented by out-of-school science learning that draws on the actual world (e.g. through fieldtrips), the presented world (e.g. in science centres, botanic gardens, zoos and science museums) and the virtual worlds that are increasingly available through information and communications technologies (ICT)
A Novel Human Cytomegalovirus Locus Modulates Cell Type-Specific Outcomes of Infection
Clinical strains of HCMV encode 20 putative ORFs within a region of the genome termed ULbβ² that are postulated to encode functions related to persistence or immune evasion. We have previously identified ULbβ²-encoded pUL138 as necessary, but not sufficient, for HCMV latency in CD34+ hematopoietic progenitor cells (HPCs) infected in vitro. pUL138 is encoded on polycistronic transcripts that also encode 3 additional proteins, pUL133, pUL135, and pUL136, collectively comprising the UL133-UL138 locus. This work represents the first characterization of these proteins and identifies a role for this locus in infection. Similar to pUL138, pUL133, pUL135, and pUL136 are integral membrane proteins that partially co-localized with pUL138 in the Golgi during productive infection in fibroblasts. As expected of ULbβ² sequences, the UL133-UL138 locus was dispensable for replication in cultured fibroblasts. In CD34+ HPCs, this locus suppressed viral replication in HPCs, an activity attributable to both pUL133 and pUL138. Strikingly, the UL133-UL138 locus was required for efficient replication in endothelial cells. The association of this locus with three context-dependent phenotypes suggests an exciting role for the UL133-UL138 locus in modulating the outcome of viral infection in different contexts of infection. Differential profiles of protein expression from the UL133-UL138 locus correlated with the cell-type dependent phenotypes associated with this locus. We extended our in vitro findings to analyze viral replication and dissemination in a NOD-scid IL2RΞ³cnull-humanized mouse model. The UL133-UL138NULL virus exhibited an increased capacity for replication and/or dissemination following stem cell mobilization relative to the wild-type virus, suggesting an important role in viral persistence and spread in the host. As pUL133, pUL135, pUL136, and pUL138 are conserved in virus strains infecting higher order primates, but not lower order mammals, the functions encoded likely represent host-specific viral adaptations
Field Research Is Essential to Counter Virological Threats
The interface between humans and wildlife is changing and, with it, the potential for pathogen introduction into humans has increased. Avian influenza is a prominent example, with an ongoing outbreak showing the unprecedented expansion of both geographic and host ranges. Research in the field is essential to understand this and other zoonotic threats. Only by monitoring dynamic viral populations and defining their biology in situ can we gather the information needed to ensure effective pandemic preparation.</p
A Dynamical Systems Model for Combinatorial Cancer Therapy Enhances Oncolytic Adenovirus Efficacy by MEK-Inhibition
Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced or metastatic cases where treatment options remain limited.National Institutes of Health (U.S.) (Grant R01 CA118545)National Institutes of Health (U.S.) (Grant R01 CA095701)National Institutes of Health (U.S.) (Grant U54 CA11297)National Institutes of Health (U.S.) (Grant U54-CA112967
Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-Ξ³
Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary
infection, establishes life-long persistence in all infected individuals. Acute
hCMV infections cause a variety of diseases in humans with developmental or
acquired immune deficits. In addition, persistent hCMV infection may contribute
to various chronic disease conditions even in immunologically normal people. The
pathogenesis of hCMV disease has been frequently linked to inflammatory host
immune responses triggered by virus-infected cells. Moreover, hCMV infection
activates numerous host genes many of which encode pro-inflammatory proteins.
However, little is known about the relative contributions of individual viral
gene products to these changes in cellular transcription. We systematically
analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major
transcriptional activator and antagonist of type I interferon (IFN) signaling,
on the human transcriptome. Following expression under conditions closely
mimicking the situation during productive infection, IE1 elicits a global type
II IFN-like host cell response. This response is dominated by the selective
up-regulation of immune stimulatory genes normally controlled by IFN-Ξ³ and
includes the synthesis and secretion of pro-inflammatory chemokines.
IE1-mediated induction of IFN-stimulated genes strictly depends on
tyrosine-phosphorylated signal transducer and activator of transcription 1
(STAT1) and correlates with the nuclear accumulation and sequence-specific
binding of STAT1 to IFN-Ξ³-responsive promoters. However, neither synthesis
nor secretion of IFN-Ξ³ or other IFNs seems to be required for the
IE1-dependent effects on cellular gene expression. Our results demonstrate that
a single hCMV protein can trigger a pro-inflammatory host transcriptional
response via an unexpected STAT1-dependent but IFN-independent mechanism and
identify IE1 as a candidate determinant of hCMV pathogenicity
Nerve-perivascular fat communication as a potential influence on the performance of blood vessels used as coronary artery bypass grafts
Virology under the microscopeβa call for rational discourse
Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns β conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we β a broad group of working virologists β seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology
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